{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,17]],"date-time":"2026-01-17T22:06:49Z","timestamp":1768687609835,"version":"3.49.0"},"reference-count":40,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,1,31]],"date-time":"2025-01-31T00:00:00Z","timestamp":1738281600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Infect. Microbiol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Vancomycin-resistant <jats:italic>Enterococcus faecium<\/jats:italic> (VRE-fm) biofilms pose a significant clinical challenge due to the limited effectiveness of traditional antibiotics. This study investigates the potential of \u03b3-linolenic acid (GLA) as a novel antibiofilm agent.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Transcriptome analysis was performed on the V27 isolate, comparing cells in mature biofilms treated with and without GLA. The findings were further validated using qRT-PCR on six VRE-fm isolates and two <jats:italic>E. faecalis<\/jats:italic> isolates.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Transcriptome analysis revealed a significant downregulation in the expression levels of genes associated with biofilm formation, including <jats:italic>fruA<\/jats:italic>, <jats:italic>fruB<\/jats:italic>, <jats:italic>sgrA<\/jats:italic>, <jats:italic>lpxtg-cwa<\/jats:italic>, <jats:italic>tfpp<\/jats:italic>, <jats:italic>lafA<\/jats:italic>, <jats:italic>lafB<\/jats:italic>, <jats:italic>malP<\/jats:italic>, <jats:italic>fsrA<\/jats:italic>, and <jats:italic>fsrC\u2019<\/jats:italic>, while a significant upregulation was observed in the expression of <jats:italic>fsrBD<\/jats:italic>. Validation by qRT-PCR in six VRE-fm isolates confirmed the significant changes in the expression levels of all genes except for <jats:italic>lpxtg-cwa<\/jats:italic>, with statistical significance. The expression of <jats:italic>bgsB<\/jats:italic> and <jats:italic>bgsA<\/jats:italic> genes, which are the homologs of <jats:italic>lafA<\/jats:italic> and <jats:italic>lafB<\/jats:italic> genes, along with the Fsr-regulated genes <jats:italic>gelE<\/jats:italic> and <jats:italic>sprE<\/jats:italic> in <jats:italic>E. faecalis<\/jats:italic>, were also found to be downregulated by GLA. In addition, KEGG analysis identified specific metabolic pathways that were significantly downregulated by GLA.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>GLA effectively targets multiple aspects of biofilm formation in VRE-fm, including the downregulation of key biofilm-related genes, the inhibition of quorum sensing systems, and the modulation of metabolic pathways. GLA emerges as a promising candidate for eradicating <jats:italic>Enterococcus<\/jats:italic> biofilms.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fcimb.2025.1525581","type":"journal-article","created":{"date-parts":[[2025,1,31]],"date-time":"2025-01-31T11:02:31Z","timestamp":1738321351000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Transcriptome analysis reveals the molecular mechanism of \u03b3-linolenic acid eradicating the biofilm of vancomycin-resistant Enterococcus faecium"],"prefix":"10.3389","volume":"15","author":[{"given":"Ming","family":"Wei","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peng","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tianmeng","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jun","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Li","family":"Gu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shuai","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2025,1,31]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms18050960","article-title":"Molecular mechanism of quorum-sensing in Enterococcus faecalis: Its role in virulence and therapeutic approaches","author":"Ali","year":"2017","journal-title":"Int. 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